Booster vaccines protect hamsters with waning immunity from Delta VOC infection, disease, and transmission

  1. Kyle G. Potts
  2. Ryan S. Noyce
  3. Chris Gafuik
  4. Cini M. John
  5. Hayley M. Todesco
  6. Elaine De Heuvel
  7. Nicole Favis
  8. Margaret M. Kelly
  9. David H. Evans
  10. Douglas J. Mahoney

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Abstract

Waning immunity to COVID-19 vaccination is associated with increased risk of breakthrough infection, especially with highly transmissible variants of concern (VOC). Booster vaccination generates rapid immune recall in humans, which real-world observational studies suggest protects against VOC infection and associated disease, and modeling studies suggest could mitigate community spread. We directly tested the impact of booster vaccination on protection against Delta VOC infection, disease, and transmission to naïve cohorts in golden Syrian hamsters. Animals with waning immunity to bnt162b2 generated rapid immune recall and strong protection against upper- and lower-respiratory tract infection when boosted with bnt126b2, mRNA-1273 or AZD1222. Boosting with either mRNA vaccine generated moderate protection against lung inflammation and virus transmission to unvaccinated animals. Our data support booster vaccination as a tool to address emerging VOC in the COVID-19 pandemic.

One-Sentence Summary

A booster vaccine delivered 9 months after primary bnt162b2 vaccination protects hamsters from Delta VOC infection, disease, and transmission.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.27.474282: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: Study design: Animal experiments and procedures were approved by The University of Calgary Health Sciences Animal Care Committee (AC20-0053) and the University of Alberta Animal Care and Use Committee (AUP00001847).
    IRB: For neutralizing antibody measurements in humans, blood was collected from healthy men (n=3) and women (n=2), mean age 44, approximately 14 days after a second dose of bnt162b2 (which was approximately 21 days after their first dose of bnt162b2) under University of Calgary Conjoint Human Research Ethics Board approval REB20-0481 and informed consent.
    Consent: For neutralizing antibody measurements in humans, blood was collected from healthy men (n=3) and women (n=2), mean age 44, approximately 14 days after a second dose of bnt162b2 (which was approximately 21 days after their first dose of bnt162b2) under University of Calgary Conjoint Human Research Ethics Board approval REB20-0481 and informed consent.
    Sex as a biological variable6–8-week-old male golden Syrian hamsters (Charles River
    Randomizationnot detected.
    BlindingAll studies were conducted by blinded experimenters.
    Power Analysisnot detected.
    Cell Line AuthenticationContamination: Cells were tested and routinely found negative for mycoplasma by Hoechst 33342 staining (Thermo Fisher Scientific) and fluorescence imaging and LookOut® Mycoplasma PCR detection kit (Sigma-Aldrich).

    Table 2: Resources

    Antibodies
    SentencesResources
    Primary antibodies used for immunohistochemistry included: Rabbit Anti-SARS-CoV-2 Nucleocapsid (Novus Biologicals, NB100-56576) and Rabbit Anti-mouse IgG Isotype Control (Novus Biologicals, NBP2-24891).
    Anti-SARS-CoV-2
    suggested: (Novus Cat# NB100-56576, RRID:AB_838838)
    Anti-mouse IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Plaque Reduction Neutralization Tests (PRNTs): For the pseudovirus PRNT assays, Vero CCL81 cells were seeded into 96-well plates at 20,000 cells/well.
    Vero CCL81
    suggested: None
    Tissue homogenates were clarified by centrifugation at 3,000 x g for 10 min, diluted in serum-free DMEM, and plated in duplicate on Vero cells in 12-well plates.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    For both pseudovirus and authentic virus PRNT assays, the dilution achieving 50% neutralization (NT50) was estimated by nonlinear regression curve fit using GraphPad Prism 9.1.1 (GraphPad Software).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analyses: Data analysis was performed using GraphPad Prism 9.1.1 (GraphPad Software).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.12.27.474282v1 on bioRxiv